HA101: Demystifying SARS-CoV-2 Testing for COVID-19-First Edition

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HA101: Demystifying SARS-CoV-2
Testing for COVID-19
April 16, 2020
First Edition
Proprietary information; Permission to use only with a reference to Health Advances as source.

Demystifying SARS-CoV-2 Testing: First Edition
2April 16, 2020
What to Expect from These Reports
What questions do you have regarding SARS-CoV-2/COVID-19 testing?
This document provides a high level, easy to read review of:
• Background on SARS-CoV-2 and its associated disease, COVID-19
• Diagnostic testing approaches and relative availability and use in the US (and elsewhere)
• Answers to many other frequently asked questions with respect to SARS-CoV-2 testing
Please email additional questions to:
diagnostics@healthadvances.com

3April 16, 2020
First Edition Agenda
• What are SARS-CoV-2 and COVID-19?
• What types of tests are used for SARS-CoV-
2/COVID-19 management?
• How is testing performed and where can I
access testing?
• Appendix and Glossary

4April 16, 2020
COVID-19 is a disease that is caused by a virus called SARS-CoV-2.
What is COVID-19?
Source: Health Advances analysis, Seattle Times.
SARS-CoV-2
Virus
Person with
COVID-19 Disease

5April 16, 2020
SARS-CoV-2 primarily infects the respiratory system and is not found in other parts of
the body.
Where in the Body Does SARS-CoV-2 Infection Occur?
Low/Non-Infected Systems
Muscle Reproductive
and Urinary
DigestiveNervousCirculatory
Skeletal
Source: Health Advances analysis, Huang 2020 Lancet.
SARS-CoV -2 Primary
Infection Locations
Respiratory
Nose
Mouth
Lungs
Throat

6April 16, 2020
Symptom
Condition
COVID-19 Cold Flu Allergies
Fever 4 2 4 2
Cough 4 3 5 3
Shortness of breath 3 1 1 4
Fatigue 3 3 4 3
Aches and pains (e.g., back pain) 2 3 4 1
Runny or stuffy nose 2 4 4 4
Sore throat 2 3 4 1
Loss of Smell/Taste 2 1 1 1
Diarrhea 2 1 3 1
Headaches 2 2 4 3
Sneezing 1 4 1 4
Itchiness 1 1 1 4
Mild forms of COVID-19 are similar to colds, flu and allergies. In other cases shortness of
breath with high fever, aches and pains, and loss of smell can be indicators.
When to Suspect SARS-CoV-2 Infection
Source: Health Advances analysis, JAMA, LA Times, WHO, CDC.
Less Common More Common

7April 16, 2020
Virus Virus Family Disease Years Active Global Cases1 Global Deaths1
SARS-CoV-2 Coronaviridae COVID-19 2019 - Present 1.9M2
123K
(~6%)2
SARS-CoV Coronaviridae SARS 2002 - 2003 8K
800
(10%)
MERS-CoV Coronaviridae MERS 2012 - Present 2K
800
(40%)
Influenza Orthomyxoviridae Flu 400 BCE - Present
1B
per year
300-650K
per year
(0.03%-0.065%)
HIV Retroviridae AIDS 1983 - Present 75M
32M
(43%)
Ebolaviruses Filoviridae Ebola 1976 - Present 31K
13K
(42%)
SARS-CoV-2 may (we are still learning about the virus) have a higher infection and
mortality rate as compared to seasonal influenza, the virus that causes the flu.
SARS-CoV-2 Compared to Other Common Viruses
1 Confirmed cases only. For SARS-CoV-2 this refers only to patients with an actual positive diagnostic test. Other diseases such as flu have been studied on an epidemiological
basis and therefore may include estimates of unconfirmed (untested) cases.
2 As of April 15, 2020; As the number of actual infections is unclear at this time, the death rate from SARS-CoV-2 is likely over estimated.
Source: Health Advances analysis, CDC, WHO.

8April 16, 2020
Feb 29, 2020
1st Reported Death
Apr 1, 2020
>1M Confirmed
Cases
The Spread of a Pandemic: SARS-CoV-2 and COVID-19 Timing
Starting with reports of a mysterious pneumonia in Wuhan, China in December, SARS-
CoV-2 spread quickly to reach 1MM global confirmed cases by April.
Source: WHO, FDA, CDC, John Hopkins CSSE.
United States
Jan 30, 2020
WHO Declares
Global Health
Emergency
Dec 31, 2019
China Alerts WHO of
Mysterious Pneumonias
World
Mar 5, 2020
>100K Confirmed
Cases
January February MarchDecember April
Mar 27, 2020
>100K Confirmed Cases
Jan 20, 2020
1st Confirmed
Case
Apr 8, 2020
>400K Confirmed
Cases
Jan 23, 2020
China Locks Down
Wuhan
Apr 8, 2020
China lifts
Wuhan
Lockdown

9April 16, 2020
There is still a lot to learn about SARS-CoV-2. The global research and clinical
communities, assisted by diagnostic testing, are working hard to address these questions.
What We Still Don’t Know, Though Some May Claim To Have the Answers
• How fast does the virus mutate?
• Will infections be seasonal?
• What is the rate of asymptomatic
cases?
• What is the mortality and
morbidity rate?
• What measures can be taken to
treat COVID-19?
• Does past infection provide
immunity to future infection?
• If so, for how long?
• What level of anti-virus antibody
confers immunity?
Note: R0 = “R naught”, the basic reproduction rate of an infection (i.e., the expected number of cases directly generated by one case in a population).
Source: Health Advances analysis.
• How contagious is the virus
(R0)?
• To what extent can the virus be
transmitted through passive
material (e.g., mail, groceries,
food delivery)?
• What measures can be taken
to more effectively limit the
spread of future outbreaks?

10April 16, 2020
• What types of tests are used for SARS-
CoV-2/COVID-19 management?
access testing?

11April 16, 2020
Multiple reasons do or could exist to perform testing for SARS-CoV-2.
Reasons to Perform SARS-CoV-2 Testing
Current and Potential Purposes of SARS-CoV-2 Testing
Diagnosis
Prognosis
• Confirm the presence of SARS-CoV-2 in patients with
symptoms
• Assessment of COVID-19 disease severity and/or risk
of progression
* Antibodies are a protein the body’s immune system produces in response to an infection. Antibodies identify the infection as foreign and direct other parts of the immune
system to attack and neutralize/destroy the infection. The presence of anti-virus antibodies does not necessarily mean a person is immune to future infection. We are still
learning about the SARS-CoV-2 immune response.
Source: Health Advances analysis, McKean, 2012 Principles and Practice of Hospital Medicine.
Patients with
Suspected Active
Infection
Exposed Individuals
and/or Those With
Known Previous
Infection
(Potential)
Immunity Status
Exposure
Screening/
Infection History
• Determine if a patient was previously infected with SARS-
CoV-2 (whether or not they had symptoms)
• Primarily for population surveillance by tracking cases
(symptomatic and asymptomatic) and exposure of those
close to known infections
• Assess the presence of (potential) immunity due to
previous infection based on presence and/or amount of
anti-SARS-CoV-2 immune response (in the form of
antibodies*)

12April 16, 2020
Clinical Reason
for Testing
What the Test Measures
SARS-CoV-2 Virus
• To confirm1 an ongoing/current infection, the virus itself must be
detected in the body
Combination of Virus,
Antibody, and Health Tests
• To date, this is unclear
• Likely a combination of virus, anti-virus immune response, and
other parameters (e.g., # of blood cells)
Anti-virus
Antibodies2
• To determine prior infection or likelihood to be immune, a test
looks for the presence of anti-virus antibodies produced by the
immune system
• The presence of anti-virus antibodies does not definitively
indicate a person is immune
Diagnosis requires detecting the virus in the body, while screening for exposure and
immunity status requires detection of anti-virus antibodies.
What Tests Measure
Diagnosis
1 Anti-virus antibody testing can also help with diagnosis, but should not be used alone for this purpose.
2 Antibodies are a protein the body’s immune system produces in response to an infection. Antibodies identify the infection as foreign and direct other parts of the immune system to
attack and neutralize/destroy the infection.
Source: Health Advances analysis, Lab Tests Online.
Exposure
Screening/
Infection History
Immunity Status
Prognosis

13April 16, 2020
Clinical Reason
for Testing
Frequency of Testing*
Reasons
Today Future Trend
4
• First priority has been diagnosing the most
severe symptomatic patients
• Control of the current outbreak, a return to
normal, and future “flu” and “covid” seasons will
require this testing
2
• Needed for a return to “normal” to enable current
and future contact tracing as well enhancing our
understanding of population exposure levels
1 Unknown
• As antibody tests become available use is
focused on determining exposure as it is not
known if antibodies confirm immunity and or at
what level (titer)
1 Unknown
• We do not yet know the best combination of tests
to inform prognostic assessment
The majority of testing today is for diagnosing an infection. Efforts are underway to begin
widespread exposure screening to help us return to “normal.”
What Testing are We Doing in the US Today?
* Based upon current events and indications from
government authorities.
Source: Health Advances analysis, press releases.
Exposure
Screening/
Infection History
Immunity Status
Diagnosis
Prognosis
Low High DecliningStableIncreasing

14April 16, 2020
The NIH recently initiated a study to quantify undetected cases of SARS-CoV-2 infection.
The study is using at-home blood collection to test 10,000 volunteers for their antibody status.
Research Initiatives for SARS-CoV-2: NIH ‘Serosurvey’
Study Purpose
• To determine how many adults in the US without a confirmed SARS-CoV-2 infection have
antibodies to the virus which indicates a prior infection and support creation of
epidemiological models to better understand how the disease spreads
Study Design
• Blood samples collected from 10,000 volunteers
• Testing for anti-SARS-CoV-2 IgG and IgM antibodies using a test developed by NIAID &
NIBIB
Who is Eligible to
Participate?
• Healthy volunteers over the age of 18 from anywhere in the US
• Individuals with a confirmed history or current symptoms of COVID-19 are not eligible
How will Samples be
Collected?
• Blood samples (80 microliters) will be collected at-home using a new blood collection
technology from Neoteryx
• Samples are shipped back in a tamper-proof pouch with no risk of transmission to mail
carriers
When Will Study
Results be Available?
• Results reported to federal public health authorities on rolling basis
• Identities of volunteers will remain private
Can I Find Out My
Results if I
Participate?
• Yes, but results will not be with rapid turnaround as investigators will provide information
only after weeks-months of analysis to confirm the tests accuracy
https://www.niaid.nih.gov/news-events/nih-begins-study-
quantify-undetected-cases-coronavirus-infection
Source: Health Advances analysis, NIAID, NIH.

15April 16, 2020
Diagnosis
Multiple measurement types, called molecular tests and immunoassays (IA), can be used
to detect virus. Immune system response requires IA to detect anti-virus antibodies.
Types of Tests that Measure SARS-CoV-2 Virus and Immune Response
1 RNA stands for ribonucleic acid. Coronaviruses RNA is the genetic information that enables the virus to replicate.
2 Viral proteins refers to any protein part of the virus itself that can be detected via an immunoassay.
Source: Health Advances analysis, Lab Tests Online.
Virus
Anti-Virus
Antibodies
What the Test is
Measuring
Type of Test
Exposure
Screening/
Infection History
Immunity Status
Immunoassay for
Viral Proteins2
Molecular Test for
Viral RNA1
Immunoassays for
Anti-SARS-CoV-2
Antibody

16April 16, 2020
Today, in the US, molecular tests are the most widely used due to higher accuracy for
diagnosis. Other types of testing are just emerging.
Most Commonly Used Tests Today in the US
More
Commonly
Used
Less
Commonly
Used
• Most accurate for identification of virus in a patient
• Primary approach to diagnosis which is the focus of
current testing in the US
• Emerging use to help assess population based exposure
and track infection
• Needed to help identify recovered patients that could
provide blood with anti-virus antibodies to ICU patients
• Can help confirm diagnosis but cannot be (should not be)
used for diagnosis alone
• Not as accurate as molecular tests for virus detection
• No tests yet available by this method (likely due to focus on
other types of tests and harder development processes)
Type of Test Rationale for Frequency of Use to Date
Immunoassay for
Viral Proteins
Molecular Test for
Viral RNA
Anti-SARS-CoV-2
Antibody
Immunoassays

17April 16, 2020
Testing is not perfect. Individual results can change over time due to disease progression
and/or be impacted by less optimal tests and testing practices.
Why Do Some Patients’ Test Results Change Over Time?
Why do some patients test negative, but eventually become positive, and
Why are some “recovered” patients testing positive again?
When are tests most accurate?
• A first test may happen when a
patients is not yet shedding virus or
enough virus to be detected
• Virus is present in many patients for
several days to a week after
symptoms resolve
• Testing is not 100% accurate, every
test (for SARS-CoV-2 or other) has an
error rate
• Even for the same method (e.g.,
molecular) performance can vary
between test manufacturers and labs
• Details of the full disease course are
not well understood yet
• In particular, we don’t know
• The timing and amount of virus
shed overtime or by severity
• How antibody-mediated immunity
develops over time
• For example, sample collection is
challenging; skills can vary between
clinical staff
Test
Timing
Clinical
Skill
The
Unknown
Test
Quality

18April 16, 2020
Clinical Reason
What Needs to
be Detected by
the Test
Relevant Sample Types
(either RNA or
viral particle
protein)
Diagnostic testing to detect the actual virus requires samples from the respiratory tract.
Anti-virus antibodies require a blood sample from your finger or vein.
Sample Types for SARS-CoV-2 Testing
Source: Health Advances analysis, CDC.
Diagnosis
Exposure
Screening/
Infection History
Bronchial
Lavage
Nasopharyngeal
(NP) Swab
Nasal
Swab
Throat
SwabVirus
Saliva or
Sputum
• Complex
• Can only be
performed in
hospital
• Intrusive
• Takes training to
collect well
• High virus amount;
best sample type
• Easier to collect
• Higher chance of missing virus due
to less virus content in sample
Whole Blood, Serum or Plasma
• Potentially more painful for
some, but provides enough
sample to quantify antibody
amounts
• Simpler to collect, but
more difficult to quantify
antibody amounts
Anti-Virus
Antibodies
Finger Stick

19April 16, 2020
SARS-CoV-2 testing is performed for a variety of clinical purposes. Today testing is
focused on diagnosis via the most widely available method, which is molecular viral RNA.
Summary of SARS-CoV-2/COVID-19 Testing
Clinical Purposes of SARS-CoV-2 Testing Relevant Test Type
• Confirm the presence of
SARS-CoV-2 in a
symptomatic patients
• Assessment of potential
COVID-19 disease
severity/disease progression
• Determine if a patient was
previously infected with SARS-
CoV-2 (whether or not they had
symptoms)
• Predict the ability of a previously
infected patient to resist future
infection based on presence of
anti-SARS-CoV-2 antibodies
Diagnosis
Prognosis
Patients with
Suspected Active
Infection
Exposed
Individuals and/or
Those With Known
Previous Infection
Immunity Status
Exposure
Screening/
Infection History
Limited Use
Today
Widespread
Use Today
Molecular
Test for Viral
RNA
Immunoassay
for Viral
Proteins
Immunoassay
for Anti-SARS-
CoV-2 Antibody
Combination of
Virus, Immunity
and Health
Tests
Immunoassay
for Anti-SARS-
CoV-2 Antibody

20April 16, 2020
access testing?

21April 16, 2020
Testing Approach
Where the Sample
is Collected
Who Collects the
Sample
Where the Testing is
Done
Examples You Might
Recognize:
Doctors office or
hospital Medical staff
At a laboratory, by certified
lab personnel
• Testing performed when
you get your blood
drawn from your arm
(e.g. cholesterol, etc.)
At (or near) a doctors
office or hospital Medical staff
Location of sample
collection, by medical staff
• Getting tested for flu or
strep at a CVS
MinuteClinic
Patient’s home Patient
At a laboratory, by certified
lab personnel
• 23andme or
AncestryDNA kits
• Cologuard for colorectal
cancer screening
Patient’s home Patient By patient at-home
• Pregnancy tests
• Glucose tests for
diabetics
Point-of-Care
At-Home
Patient Self-
Collection
At-Home
Patient Self-Test
Lab Testing
Testing can be supported by various formats, which differ primarily by 1) Where and by
whom the sample to be tested is collected, and 2) Where the testing is conducted.
Testing Approaches

22April 16, 2020
Not Available Today
Not Available Today
A patient’s experience with SARS-CoV-2 testing varies depending on the testing approach
used.
SARS-CoV-2 Testing Journey by Test Approach
Testing Approach What Happens
Sample Collected
Outside/Drive
Through
Collect
Sample
at Home
Physician
Orders Test
(Telehealth or
in person)
Lab Performs
Test
Physician
Interprets
Results
Sample Transported to Lab
On-site lab: Hours-1 Day
Off-site lab: Hours- 2 Days
Results in
5-45 min
Results in
Hours-
Days
Physician
Orders Test
(Telehealth or
in Person)
Sample
Collection Kit
Sent to
Patient’s Home
Lab Performs
Test Physician
Interprets
Results
Lab Testing
Point-of-Care
At-Home Patient
Self-Collection
At-Home Patient
Self-Test
Patient with
Suspected
COVID-19
Test Performed Near
Patient
Telehealth
Follow-up
Purchase
OTC Test
Patient Mails
Sample to
Lab
Telehealth
Follow-up
Patient
Performs
Test at Home
Patient
Interprets
Results
Patient with
Suspected
COVID-19
TBD, est.
5-45 min
Results in
Days
Inside Care
Facility
Medical
Personnel
Collects

23April 16, 2020
POC tests for SARS-CoV-2 can be performed at physician offices and hospitals with CLIA
waived certificates. In the future, it may be performed at your home or even your workplace.
Where Can POC Testing Be Performed?
POC
Testing
Locations
At-Home/
Patient Self Test
Physician Offices
with CLIA waived
Certificates
Clinics (e.g., Retail
Clinics, Urgent
Care)
Potential New
Sites for
Return to Work
Hospitals with
CLIA waived
Certificates
Common
POC Tests
Today
• Glucose
monitoring for
diabetes
• hCG (pregnancy
tests)
• Influenza
• HbA1c
• HIV
• Influenza
• Strep
• Lipids
• Potential new
sites; no testing
yet
• Influenza
• Blood gases
• Electrolytes
• Hematocrit
SARS-CoV-
2 Testing
Today
X  X X 
Future
SARS-CoV-
2 Testing
    
Examples
Used Today
BD Veritor
(Rapid
Test Reader)
Abbott
i-Stat
Glucose Meters
Alere Influenza
Rapid Test
Alere epoc
Pregnancy Test

24April 16, 2020
Test Approach
Current Use for SARS-CoV-2
Diagnosis
Exposure Screening/
Infection History
4 2
Vast majority of testing
(molecular testing)
Still early days of use
(serology testing)
2 1
Beginning to be used early-April No tests yet authorized by FDA
“At this time, the FDA has not authorized any test that is available to purchase for
testing yourself at home for COVID-19…We are actively working with test
developers in this space.” – FDA, March 20, 2020
Currently, only lab and POC tests are available for SARS-CoV-2 in the US, though some
companies are developing at home self-collection or self-testing options.
Current US Testing Approaches for SARS-CoV-2
Less
Common
More
Common
Point-of-Care
(POC)
At-Home Patient
Self-Collection
At-Home Patient
Self-Test
Lab Testing
Source: Health Advances analysis, FDA, company websites, GenomeWeb, FierceBiotech.

25April 16, 2020
No single test format offers the perfect approach for SARS-CoV-2 testing.
SARS-CoV-2 Test Formats: Advantages and Disadvantages
Test Feature/Impact
Degree to Which Each Test Format Meets Test Feature
Rationale
Worst Best
Fast Time to Test
Results
(From Patient
Presentation)
Slower Fastest
• At-home methods provide
immediate results, but require
time to ship the collection kit
or test to the patients’ home
Help with Social
Distancing
Least Most
• Unknown if there is potential
for an at-home collection kit
sent to a lab to increase
spread through couriers/mail
Tests per Hour Least Most
• Laboratory platforms support
automated high-throughput,
upwards of 30-50x the
tests/hour of point-of-care
Sample Quality Lowest Highest
• Some sample types currently
being used are difficult for
patients to reliably collect at
home (e.g., nasopharyngeal
swab)
Accurate Interpretation
of Results
Least Most
• Concern over ensuring
patients accurately interpret at
home test results and follow-
up with doctors
* If the POC or over the counter test requires an instrument to read the results, tests per hour are limited by the TAT of the test as only one test can be run per instrument at a time.
If there is no instrument reader, tests per hour are essentially unlimited though could only scale based on the number of tests available and timing of sample collection.
* *

26April 16, 2020
Consult the CDC and your local doctor for medical advice if you, or anyone in your care, is
experiencing symptoms.
What Should I Do If I’m Having COVID-19 Symptoms?
The CDC’s online Self-
Checker can help you
make decisions to seek
appropriate medical care
for you and anyone in
your care
https://www.cdc.gov/coronavirus/2019-ncov/
Source: Health Advances analysis, CDC.

27April 16, 2020
Relative Access to SARS-CoV-2 Testing
Where You Can Go
(After Talking To Your Doctor)
Per CDC guidelines, testing is only recommended
for priority cases and not yet broadly available due
to limited testing capacity (though expansion is
happening quickly)
1. Local Hospitals/ERs
2. Your Doctor’s Office
3. Retail Clinics
4. And Soon PharmaciesCall your Doctor if you believe you are experiencing
symptoms of COVID-19
The FDA has not yet authorized use of at-home sample collection or testing methods for
SARS-CoV-2 diagnosis
Be wary of online vendors offering test kits, as these are likely fraudulent
Their use could pose public health risks
Because testing for SARS-CoV-2 is not broadly available today, to determine where you
can personally go to get tested, if needed, start by calling your personal doctor.
Where Can You Access SARS-CoV-2 Testing Today?
Source: Health Advances analysis, CDC, FDA.
! !
Point-of-Care
At-Home
Patient Self-
Collection
At-Home
Patient Self-
Test
Lab Testing

28April 16, 2020
Insurance Type
Test Reimbursement
(Paid from Insurer to a
Lab)
Cost of Test
(Paid from Lab to
Manufacturer)
Patient Cost-
Sharing/Out of
Pocket Cost
Details
• CDC test = $36
• Non-CDC Test = $100*
$20-$40 $0
• CMS announced they will cover
SARS-CoV-2 testing for all Medicare
and Medicaid patients
• Negotiated Price or
Cash Price on Website
$20-$40 $0
• The CARES Act forces private
insurance companies to cover all
eligible SARS-CoV-2 tests at the
negotiated or listed price
• This requirement is in effect until the
end of the public health emergency
• CDC test = $36
• Non-CDC Test = $51
$20-$40 Most Likely $0
• HHS Secretary Alex Azar claims part
of the $100B in funding for hospitals
and HCPs will go to paying for
testing and treatment of uninsured
patients
The CARES Act, signed March 27, provides funding for uninsured patients to receive
testing and requires private insurers to cover the test at negotiated prices.
How Sars-CoV-2 Testing is Paid For
Future Steady-State of Reimbursement
• Reimbursement for future SARS-CoV-2 molecular assays will likely be similar to molecular flu test reimbursement today
with a price between $90-$100 and wide coverage from both CMS and private insurers
Medicare/
Medicaid
Private
Insurance
Uninsured
* On April 14th, CMS announced that Medicare will pay a higher amount of $100 for COVID-19 Dx tests using high-throughput technologies (>200 samples/day), lower-throughput
testing will remain at the $51 per test rate.
Note: CMS = Centers for Medicare and Medicaid.
Source: Health Advances analysis, news reports, CARES Act, CMS.

29April 16, 2020
Our next edition will address the following questions:
Second Edition Agenda
• What does it take to operationalize testing?
• What tests are available for SARS-CoV-2 testing in
the US today? In other geographies?
• What went well and what didn’t in establishing US
testing?
• What is the future testing outlook?

30April 16, 2020
access testing?

31April 16, 2020
Mild forms of COVID-19 have symptoms similar to the seasonal flu while severe forms
have more intense respiratory symptoms or even septic shock.
Symptoms of SARS-CoV-2/COVID-19
Source: Health Advances analysis, LA Times.

32April 16, 2020
Similar to SARS-CoV (the virus that causes the disease SARS), SARS-CoV-2 enters human
respiratory cells to produce new viral particles that are then released to infect other cells.
SARS-CoV-2 Life Cycle
Source: Health Advances analysis, Du Nat Rev Micro 2009.

33April 16, 2020
Immunity to viruses develops through a complex chain of events that leads to antibodies.
Whether or not SARS-CoV-2 antibody provides immunity at all or that will last is not known.
Understanding the Immune Response and Response (Antibody) Testing
Source: Health Advances analysis, Johns Hopkins Health Medicine.
SARS-
CoV-2
• Body forms initial
antibodies that
circulate in the body
and help fight the virus
• Presence of IgM
antibodies in a test
indicate a recent or
active infection
• Over time the body
develops memory cells
that produce
antibodies faster in
case of future infection
• IgG antibodies in a test
indicate a previous
infection and possible
immunity
Overly Simplified Representation of the Antibody Immune Response
Initial Infection Days to Week+ Week+ Months to Years
• Ability to form immunity
varies by pathogen
• In some cases viruses
quickly mutate making
existing immunity irrelevant
• In other cases antibody
levels naturally decline or
viruses have mechanisms
to evade antibody based
immunity
• We do not know how
SARS-CoV-2 immunity will
progress
IgM
Antibodies
IgG
Antibodies
Possible Immunity

34April 16, 2020
The NIH recently initiated a study to quantify undetected cases of SARS-CoV-2 infection. The
study is using at-home blood collection to test 10,000 volunteers for their antibody status.
NIH SARS-CoV-2 Epidemiology Research Study
10,000 healthy volunteers from
throughout the US. To be eligible, you
cannot have a confirmed history of
COVID-19 nor currently have symptoms
consistent with COVID-19
Enrolled participants will have a
virtual clinic visit with the NIH,
complete a health assessment
questionnaire and provide basic
demographic information
Participants will self-collect their
blood-sample using Neoteryx’s home
blood collection kit and ship back to the
NIH for testing
Study results will be reported to
federal public health authorities on
a rolling basis to support
epidemiological modeling efforts
to inform public decision making
Note: NIAID= National Institute of Allergy and Infectious Diseases. NIBIB= National Institute of Biomedical Imaging and Bioengineering (NIBIB).
Source: Health Advances analysis, NIAID, NIH.
NIH will analyze the blood samples for
anti-SARS-CoV-2 antibodies IgG and
IgM using an ELISA assay developed
by researchers at the NIAID and NIBIB
Results upon request will be provided
back to participants. Participants should
not expect rapid turnaround, as it will
only be provided after weeks or
months of analysis to confirm the
test’s accuracy
Study Design

35April 16, 2020
Glossary
Term Definition
Academic
A noncommercial research environment, focused on the goal of advancing our collective scientific knowledge
base.
Assay The procedure used for conducting a diagnostic test.
Analyte Entity or target that is being analyzed. Can be an ion, a protein, a cell, a molecule, etc.
Automation Line
A track system moving samples between instruments as opposed to a “sneaker network” which is technicians
moving samples through the lab.
Biomarker
A biological marker of disease. Technically all diagnostics are measuring biomarkers but in market
terminology this refers to novel markers linked to personalized medicine.
CLIA Waiver
Tests receiving a CLIA waiver are low complexity and can be performed by a healthcare worker with no
diagnostic training or experience or by the patient themselves. CLIA waivers are a requirement for POC or
NPT and apply to the US only.
Clinical Laboratory
Improvement Amendments
(CLIA)
CLIA of 1988 created quality standards for all US laboratory testing to ensure accuracy, reliability and
timeliness regardless of where the test was performed.
Each specific laboratory test system, assay, and examination is graded for level of complexity by assigning
scores of 1, 2, or 3 (1 indicates the lowest level of complexity, and 3 indicates the highest level) for each of the
following seven criteria: Knowledge; Training and experience; Reagents and materials preparation;
Characteristics of operational steps; Calibration, quality control, and proficiency testing materials; Test system
troubleshooting and equipment maintenance; Interpretation and judgment.
High complexity tests are performed in specialty laboratories. Moderate complexity tests are performed in
hospital, reference or physician office laboratories by trained laboratory technicians. Low or CLIA waived tests
are typically performed at the point of patient care and can be performed by untrained personnel or even by
the patient.

36April 16, 2020
Glossary
Term Definition
Companion Diagnostics
(CDx)
(HA definition) Diagnostic tests which are used in combination with a specific therapy in order to guide treatment decisions.
(FDA definition) In vitro diagnostic device or imaging tool that provides information that is essential for the safe and
effective use of a corresponding therapeutic product. The joint application of the diagnostic test and therapeutic are
explicitly described in the product labels.
Core Lab
Hospital laboratory staffed by minimally trained lab technicians performing high volume, moderately complex tests on
highly automated instruments.
Cost per Reportable
A method of financing the cost of an instrument and reagents. Total laboratory costs for running an assay divided by the
number of results obtained. This spreads out the cost of “non-reportable” results (caused by either sample or analysis
error) over all of the useful results.
Emergency Room (ER)
Emergency room (ER) is the area in a hospital where patients present, are evaluated, and are often treated in an
emergency situation.
(FDA) IVD
• The mark given to in vitro diagnostic (IVD) products indicating that the product has been cleared (510k) or approved
(PMA) for use as a diagnostic product in the US
• Manufacturers can market these products to labs for the specific claims included in the product label
Grant/Research Grant
Non-repayable funding provided by an agency, foundation, trust, or other entity. Typically provided to fund a specific
project or objective as outlined in a grant proposal. See R01.
Hospital Near Patient
Testing (NPT)
Testing performed outside of the laboratory, near to the patient in a hospital. These tests are rapid and include both
handheld readers and benchtop analyzers.
Immunoassay (IA)
A discipline of clinical laboratory medicine in which antibodies are used to detect target analytes from body fluids primarily
blood. A number of different IA methods are available. IA is typically performed on highly automated instrumentation.
Industry
A commercial research environment, focused on the goal of developing new products or services which enhance health
but also generate financial returns.
Information Technology
(IT)
Technology that encompasses the computer systems and software that control instrumentation as well as results reporting
and connections of the lab instruments to the laboratory information system (LIS) and hospital information system (HIS).
Installed Base Total number of actively used instruments of a particular type among a group or multiple groups of customers.

37April 16, 2020
Glossary
Term Definition
Integrated Hospital Network
(IHN; IDN)
A group or system of hospitals and clinics operating jointly to serve their patients. Buying decisions are
often made for the entire system at once to provide power in price negotiations with vendors and
standardize equipment and products used across the system. These relatively small groups typically drive
compliance more effectively than GPOs. Alternatively called an Integrated Delivery Network (IDN).
Intended Use/Indications for
Use
Device classification depends on the intended use of the device and also upon indications for use. For
example, a scalpel's intended use is to cut tissue. A subset of intended use arises when a more
specialized indication is added in the device's labeling such as, "for making incisions in the cornea".
Indications for use can be found in the device's labeling, but may also be conveyed orally during sale of
the product. the term intended use means the general purpose of the device or its function, and
encompasses the indications for use. The term indications for use, as defined in 21 CFR 814.20(b)(3)(i),
describes the disease or condition the device will diagnose, treat, prevent, cure or mitigate, including a
description of the patient population for which the device is intended.22
Integrated Platform An automated analyzer that has the capability to run both clinical chemistry and immunoassay tests.
Intensive Care Unit (ICU)
Intensive care unit (ICU) is the area in a hospital where patients in critical conditions are treated and
monitored.
In-Vitro Diagnostics (IVD) or
Clinical Diagnostics Market
In Vitro Diagnostics
Services or products including instruments and reagents that utilize a variety of methods and formats to
perform tests on human samples outside the body in order to assess disease risk, diagnose a condition,
or monitor a patient’s health
IVDMIA
In Vitro Diagnostics Multivariate Index Assays: Use multiple molecular and non-molecular markers to
produce a diagnostic, prognostic and/or predictive index (value) for a patient. Example IVDMIA: Agendia’s
Mammaprint, a 70-gene, tissue-based assay to determine the risk of breast cancer recurrence post
surgery
IVD Supplies Market
Revenues derived by vendors from sale of instruments, reagents, and service provided to clinical
laboratories for IVD purposes.

38April 16, 2020
Glossary
Term Definition
(FDA) IVD
The mark given to in vitro diagnostic (IVD) products indicating that the product has been cleared (510k) or
approved (PMA) for use as a diagnostic product in the US.
Manufacturers can market these products to labs for the specific claims included in the product label
Kit
A set of reagents manufactured and packaged together for a specific purpose or to detect a specific
analyte. Kits can come in RUO or IVD form. These are sold to labs that perform the testing.
Laboratory Developed Test
(LDT)
A test that is developed and validated within a single laboratory and is not sold as a diagnostic kit for other
labs to perform. These tests are not approved by the FDA, but rather, are regulated by CLIA (for
accuracy, precision, test sensitivity and specificity). These tests may utilize CE and FDA IVD marked
products or RUO products to perform the test. In the US, labs must be CLIA certified to perform such
testing.
Laboratory Testing Market
Revenues derived from laboratories performing tests (includes hospital and reference laboratories as well
as certified physician office laboratories; does not include near-patient or patient self-testing). By
definition, these tests are performed by trained lab personnel and are not CLIA waived. The costs (IVD
Supplies Market Revenue) are inherently captured in this revenue.
Microbiology
A discipline of clinical laboratory medicine used to detect the presence of pathogens in bodily tissues.
Performed in a specialty laboratory with a low level of automation. Testing involves slow culture-based
(measurement of pathogen growth over time) testing methods.
Molecular Diagnostics (MDx)
A discipline of laboratory medicine involving the use of testing procedures to measure DNA and/or RNA
Despite being measures of molecules, other testing disciplines that assess proteins etc. are NOT
considered to be MDx by standard industry terminology. For example, if you ask a lab director if they
perform molecular testing, if they are not doing DNA or RNA analysis they will say no. In addition,
molecular labs perform only or mostly DNA/RNA analysis methods
Multi-analyte Test
Type of multiplexing in which multiple analytes are measured and each analyte measured corresponds to
one distinct diagnostic answer.

39April 16, 2020
Glossary
Term Definition
Multi-analyte Technology
A single platform, instrument, box, or technology that can measure more than one type of analyte at a
time with analytes defined as nucleic acids, proteins, lipids, ions, cells, etc.
Multiplexed Test/Technology
Technical definition: Simultaneous measurement of multiple target analytes in a single reaction vessel.
Broader market definition: In the marketplace, some technologies that take a single sample input and split
that sample (via automation or microfluidics) into individual reaction vessels to perform multiple tests are
also considered to be “multiplex” technologies.
Near-Patient Testing (NPT)
Market
Revenues derived by vendors from sale of IVD supplies outside the laboratory within the hospital
setting. This does not include point-of-care (POC) testing in the physician office. Tests performed
in this setting are rapid and must be CLIA waived. They are performed by nurses and physician
rather than by trained laboratory professionals.
National Institute of Health
(NIH)
A US government agency dedicated to medical innovation. The largest public funder of
biomedical research in the world.
Novel Content Newly discovered analytes or biomarkers.
Patient Self Testing (PST)
Test performed by the patient. Most PST is performed for glucose monitoring at home. All are
CLIA waived.
Physician Office
Laboratory (POL)
Laboratory associated with large physician practices performing non-CLIA waived tests. POC
testing can also be performed in a physician office but this is not considered laboratory testing.
Point-of-Care (POC)
Market
Revenues derived by vendors from sale of IVD supplies to be used outside of the laboratory. The
POC market includes professional POC and patient self testing revenues. Tests are performed
either by a healthcare worker or patient. All are CLIA waived.

40April 16, 2020
Glossary
Term Definition
Pre- and Post- Analytic
Automation
Pre-analytic automation is instrumentation which automates single or multiple steps in the
preparation of a sample for testing, including sample sorting, centrifugation, de-capping, and
aliquotting.
Post-analytic automation is instrumentation which automates single or multiple steps in the
processing of a sample after testing, including re-sorting, storage, and retrieval.
Professional POC
Testing performed at the point of patient care by trained healthcare worker. This includes hospital
near patient testing and physician office POC testing. (POL testing is included in the Laboratory
Testing Market)
R01
The most common type of grant awarded by the NIH. Used to support a specific investigator and
research program for 3-5 years. Awarded for research which represents the investigators’
specific interests and competencies and that falls within the mission of the participating NIH
Institutes and Centers.
Random Access
Instrumentation
Ability to add samples to an instrument at any time without disrupting on-going testing. Each
sample can be tested in its own way: Number of tests, type of test (single analyte or multiplex),
and specific test(s) performed. Instrument software prioritizes which samples get what test in
what order to maximize instrument throughput and minimize TAT.
Random Manual Assays
Tests which due to low volume and esoteric nature will never be automated and will always be
performed manually.
Reference Lab
Commercial service organizations offering routine and esoteric laboratory services to physician
offices, clinics, and hospitals.

41April 16, 2020
Glossary
Term Definition
Research Group
Two or more investigators of any tenure or level of experience using shared resources and
funding in support of a common mission and goal. Colloquially referred to as a “lab”.
Research Use Only (RUO)
A mark given to products indicating that product has NOT been given clearance or approval to
be used for clinical purposes.
In the US, manufacturers cannot market these products to clinical labs or help them develop
tests in their labs that use these products.
Sample to Result
Automation/Processing
A fully automated instrument which allows the operator to input a sample and walk away. The
instrument returns a result with no further intervention.
Specialty CLIA Lab
A term used for two purposes:
(More common) to describe a service organization performing proprietary tests (e.g.
OncotypeDx) but not performing routine testing.
(Less common) to describe divisions of the hospital laboratory performing complicated testing
requiring highly trained laboratory technicians. Specialty labs within the hospital include:
anatomical pathology labs, microbiology, molecular and blood banks.
Turnaround Time (TAT)
The time it takes to return a result, either within the context of an instrument or of the whole
laboratory procedure, beginning with the sample being loaded onto the instrument and ending
with the result being recorded on the instrument. This can also be called the time to result.
An alternative definition, not used in this presentation, is the total time it takes from sample
acquisition to the time the result reaches the ordering physician.

42April 16, 2020
Health Advances Diagnostics Leadership Team
• Donna Hochberg joined Health Advances in 2005 and
leads the firm’s Diagnostics and Life Science Tools
Practice.
• Her work includes application prioritization, launch
strategy, corporate strategy, deal diligence, and
international and domestic market analysis using both
qualitative and quantitative approaches. Her clients
offer products and services in personalized medicine,
point-of-care, mainstream clinical diagnostic, and life
science tools and range from small diagnostics and
tools start-ups to the largest public companies and non-
profit institutions in the industry.
• Prior to joining Health Advances, Donna worked as a
scientist at One Cell Systems and Iquum developing
diagnostics for oncology and infectious diseases. She
received her Bachelors degree in Biology from the
University of Illinois at Urbana-Champaign and her
Ph.D. in Immunology from the Sackler School of
Biomedical Sciences at Tufts University
• Gary Gustavsen came to Health Advances in 2005
and leads the Personalized Medicine Practice at
Health Advances. His work focuses on
commercialization strategy, indication prioritization,
pricing and reimbursement strategy, system
economics, and business development opportunities
for both diagnostic and therapeutic clients.
• Prior to joining Health Advances, Gary was a
researcher at Brookhaven National Lab evaluating a
proprietary line of synthetic growth factors. Gary also
worked in the Cell & Tissue Technologies group at
Becton Dickinson, the Exploratory Cancer Research
group at OSI Pharmaceuticals, and most recently the
Corporate Strategy group at Millennium
Pharmaceuticals. Gary received his Bachelors
degree in Biomedical Engineering from Duke
University and his Masters degree in Biomedical
Engineering from Stony Brook University.
Donna Hochberg, PhD
Partner
Gary Gustavsen
Partner and Managing Director

43April 16, 2020
Kristen Amanti, PhD
Vice President
Peter Origenes
Vice President
Kristine C. Mechem PhD
Vice President
• Kristen Amanti joined the Health Advances
team in 2010 and is a leader in the
Reproductive and Genomic Health practice
and Personalized Medicine practice. She
has deep experience in commercialization
strategy, business development opportunity
assessment, deal diligence, international
and domestic market assessment, corporate
strategy, and is a seasoned workshop
facilitator. She has content expertise in
companion diagnostics, reproductive and
prenatal health, genomic health, cancer
screening, tumor genetics and oncology.
• Prior to joining Health Advances, Kristen
received her PhD in Cancer Pharmacology
from Dartmouth College where her research
focused on the development of novel
targeted cancer therapeutics. She received
her Masters degree in Cell and Molecular
Biology and Bachelors degree in Biology
from the University of Vermont.
• Peter Origenes brings over 30 years of
healthcare experience to Health Advances,
including as a corporate executive, principal
investor, and strategy consultant across
diagnostics, life science research products,
medical devices, and biopharmaceuticals.
• Prior to joining Health Advances, Peter held
executive positions at Becton Dickinson,
GE Healthcare, and Ortho Clinical
Diagnostics. Prior to that, he was a partner
at Radius Ventures, and a consultant with
The Wilkerson Group and Bain.
• Peter holds a Master of Science in
Industrial Administration from the Tepper
School at Carnegie Mellon University, and
Bachelor’s degrees in Genetics and History
from the University of California, Berkeley.
• Kristine Mechem has over 15 years of life
science experience across diagnostics,
medical devices and therapeutics. Her
experience spans the full continuum of
commercial activities from market planning
to sales force effectiveness. She has
expertise in portfolio prioritization, product
requirements, asset opportunity
assessments and launch planning.
• Most recently she was the commercial
head of a micro-cap molecular diagnostic
company. At OncoCyte, she helped to take
the company public, served as a corporate
officer and led the development of the
commercial plan. She has also held
positions at Abbott, Genentech and The
Zitter Group
• Kristine received her PhD in Sociology from
the University of Chicago. She is an active
member of Women In Bio.

44April 16, 2020
• Arushi Agarwal joined the Health Advances
team in 2011 and spends the majority of her
time working in the Diagnostics and Life
Sciences Practice. She has expertise in M&A
due diligence and global commercialization
strategies for diagnostics. Arushi’s specific
areas of focus include companion
diagnostics, point-of-care diagnostics and
liquid biopsy testing.
• Prior to joining Health Advances, Arushi
received her Masters in Biomedical
Engineering from Columbia University and
Bachelors in Biology from the Massachusetts
Institute of Technology.
• Daniela is an experienced team leader with expertise
in opportunity assessment, global commercialization
strategy, market access, and business model
evaluation across diagnostics and life sciences
products. Daniela’s diverse experience in the
diagnostics and life sciences tools space provides a
strong base to help generate actionable growth
strategies for clients.
• Prior to joining Health Advances, Daniela helped
clients in the healthcare industry optimize their value
proposition and global market access strategies to
enable product adoption.
• Daniela earned her PhD in Chemistry, summa cum
laude, from the University of Basel, Switzerland and
her MBA from Johnson Graduate School of
Management at Cornell University.
Arushi Agarwal
Vice President
Daniela Hristova-Neeley, PhD
Director

45April 16, 2020
Health Advances Diagnostics Team
Ravi Amin
Engagement Manager
Kelsey Taylor, PhD
Engagement Manager
Emily Kong
Consultant
• Ravi Amin joined Health Advances in
2014 and is an experienced team leader
in the firm’s Diagnostics and Life Science
Tools Practice.
• His experience includes opportunity
assessment, commercialization strategy,
and market analysis using both qualitative
and quantitative approaches. He also has
experience developing strategies for
companies ranging in size from start-ups
to large public companies.
• Prior to joining Health Advances, Ravi
worked at Beckman Coulter in a variety of
roles across corporate strategy and
strategic marketing. He received his
Bachelors in Genetics from the University
of Georgia and his Master of Business
and Science at the Keck Graduate
Institute of Applied Life Sciences
• Kelsey Taylor joined the Health Advances
team in 2016 and is an experienced team
leader across Health Advance’
Diagnostics, Biopharma, and Precision
Medicine Practices.
• Kelsey’s experience includes opportunity
assessment, business model evaluation,
and commercialization strategy
development for novel diagnostics.
• Prior to Health Advances, Kelsey received
her PhD in Biological and Biomedical
Sciences at Harvard University and
Bachelors in Biochemistry, Cellular and
Molecular Biology from Connecticut
College.
• Emily Kong joined Health Advances in
2016 and is a team leader across firm’s
Diagnostics, Digital Health, and Precision
Medicine Practices
• Her experience includes development and
commercialization strategy, competitive
assessment, market sizing, and revenue
forecasting with a content focus in several
areas including oncology, precision
medicine, traditional laboratory
diagnostics, and rare diseases
• Prior to joining Health Advances, Emily
received her Bachelors in Biology and
Economics from Dartmouth College

46April 16, 2020
Health Advances Diagnostics Team
John Latimer
Senior Analyst
Aaron Dy, PhD
Senior Analyst
Emily Berghoff, PhD
Senior Analyst
Alexis Froistad
Analyst
• John Latimer joined Health
Advances in 2018 and works
primarily in the firm’s
Diagnostics and Life Sciences
practice.
• He has experience in strategy
development, international
and domestic market analysis,
M&A diligence, and
opportunity assessment of
emerging technologies.
• Prior to joining Health
Advances, John graduated
from Stanford University with a
B.S. in Biology. He held
several research positions
during his time at Stanford
including as a clinical
researcher in the Department
of Cardiovascular Medicine.
• Aaron Dy joined Health
across healthcare practices,
with a particular focus in the
Diagnostics and Life Sciences
Tools practice.
• His experience includes
competitive assessment,
commercial strategy, product
positioning strategy, survey
design, and revenue
forecasting.
• Prior to Health Advances,
Aaron received his Bachelors
degree in Applied Physics
from Indiana University and
his PhD in Biological
Engineering from the
Massachusetts Institute of
Technology.
• Emily Berghoff joined Health
across the firm’s Diagnostic,
MedTech, and BioPharma
practices.
• Her experience includes
opportunity assessment,
commercialization strategy,
market analysis, and revenue
forecasting.
Emily worked at Exosome
Diagnostics developing
assays for oncology. She
received her PhD in Biological
Sciences from Columbia
University and her Bachelors
degree in Chemistry from
Colby College.
• Alexis Froistad joined Health
across healthcare practices,
with a focus in the Diagnostics
and Life Sciences Tools
practice.
• Her experience includes
product positioning strategy,
franchise development
strategy, market analysis, and
survey design.
Alexis graduated from
Stanford University with a B.S.
in Human Biology. She held a
long-term research position in
the Stanford Parker Center for
Allergy and Asthma Research
studying pulmonary arterial
hypertension.

47April 16, 2020
Contact Information
Donna Hochberg, PhD
Partner
dhochberg@healthadvances.com
Gary Gustavsen
Partner
ggustavsen@healthadvances.com
Kristen Amanti, PhD
Vice President
kgamanti@healthadvances.com
Arushi Agarwal
Vice President
aagarwal@healthadvances.com
Kristine Mechem, PhD
Vice President
kmechem@healthadvances.com
Peter Origenes
Vice President
porigenes@healthadvances.com
Health Advances LLC
275 Grove Street
Suite 1-300
Newton, MA 02466
781-647-3435
www.healthadvances.com

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